EP1516880B1 - Phosphines chirales pour utilisation en synthèse asymétrique - Google Patents

Phosphines chirales pour utilisation en synthèse asymétrique Download PDF

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EP1516880B1
EP1516880B1 EP04021174A EP04021174A EP1516880B1 EP 1516880 B1 EP1516880 B1 EP 1516880B1 EP 04021174 A EP04021174 A EP 04021174A EP 04021174 A EP04021174 A EP 04021174A EP 1516880 B1 EP1516880 B1 EP 1516880B1
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Prior art keywords
bis
diyl
biphenyl
dichloro
phosphine
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EP1516880A1 (fr
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Dieter Prof. Artl
Benjamin Dr Meseguer
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Boehringer Ingelheim International GmbH
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
    • C07F15/0046—Ruthenium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/5027—Polyphosphines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
    • C07F9/5329—Polyphosphine oxides or thioxides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/60—Reduction reactions, e.g. hydrogenation
    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/60—Reduction reactions, e.g. hydrogenation
    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/645—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of C=C or C-C triple bonds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
    • B01J2531/0266—Axially chiral or atropisomeric ligands, e.g. bulky biaryls such as donor-substituted binaphthalenes, e.g. "BINAP" or "BINOL"
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/821—Ruthenium

Definitions

  • the present invention relates to biaryl bisphosphines and intermediates thereof. Furthermore, the scope of the invention comprises catalysts producible from the biaryl bisphosphines and their use in asymmetric syntheses.
  • Enantiomerically enriched biarylbisphosphines especially those derived from substituted binaphthylene and biphenylene, often lead to good to very good enantioselectivity as ligands of transition metal complex catalysts (see, for example, US Pat Helv. Chim. Acta 1988, 71, 897-929 ; Acc. Chem. Res. 1990, 23, 345-350 ; Synlett 1994, 501-503 ; Angew. Chem. 2001, 113, 40-75 ).
  • the number of such industrial processes is limited so far because the number of ligands available that can be widely used for a larger number of substrates is small. Rather, the extensive investigations in this area show that, because of the substrate specificity of the catalyst, which is often tailor-made for a very specific substrate, even slight changes within the same substrate group can not achieve the required enantiomeric purity for a very similar product.
  • EP-A 643,065 and EP-A 749 973 are representatives of substituted in 5,5'- and 6,6'-position biphenylbisphosphines known by varying the Phosphansubstituenten allow adaptation of the catalysts obtainable from these ligands to particular substrates so as to achieve optimized enantioselectivities.
  • the invention encompasses both stereoisomerically enriched compounds of the formula (I) and optically non-active mixtures of compounds of the formula (I).
  • Optically non-active mixtures of compounds of the formula (I) are, in particular, racemic mixtures or, in the presence of diastereomers, mixtures of racemic mixtures
  • an ee of 80% or more more preferably an ee of 90% or more, and most preferably especially an ee of 98% or more.
  • a molar stereoisomeric purity of 99.5% and more or an enantiomeric purity of 99% ee or more the terms stereoisomerically pure or enantiomerically pure are also used.
  • Alkyl is, for example and preferably, unbranched, branched, cyclic or acyclic C 1 -C 12 -alkyl radicals which may be either unsubstituted or at least partially substituted by fluorine, chlorine, or unsubstituted or substituted aryl, or C 1 -C 6 -alkoxy.
  • Alkyl is particularly preferably branched, cyclic or acyclic C 1 -C 12 -alkyl radicals which are not further substituted.
  • Aryl is, for example, carbocyclic aromatic radicals having 6 to 18 skeletal carbon atoms or heteroaromatic radicals having 5 to 18 skeletal carbon atoms, in which none, one, two or three skeletal carbon atoms per cycle, in the entire molecule at least one skeleton carbon atom, by heteroatoms, selected from the group nitrogen, sulfur or oxygen, may be substituted.
  • carbocyclic aromatic radicals or heteroaromatic radicals may be substituted with up to five identical or different substituents per cycle, selected from the group free or protected hydroxy, iodine, bromine, chlorine, fluorine, cyano, free or protected formyl, C 1 -C 12 -alkyl such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, tert-butyl, cyclohexyl, n-hexyl, n-octyl or iso-octyl, C 6 -C 12 aryl, such as for example, phenyl, C 1 -C 6 alkoxy, tri (C 1 -C 6 alkyl) siloxyl, such as trimethylsiloxyl, triethylsiloxyl and tri-n-butylsiloxyl.
  • substituents per cycle selected from the group free or protected hydroxy, iodine, bro
  • carbocyclic aromatic radicals having 6 to 18 skeleton carbon atoms are, for example, phenyl, naphthyl, phenanthrenyl, anthracenyl or fluorenyl, heteroaromatic radicals having 5 to 18 skeletal carbon atoms in which none, one, two or three skeletal carbon atoms per cycle, but at least one skeletal carbon atom in the entire molecule
  • pyridinyl, oxazolyl, thiophenyloxy, benzofuranyl, benzothiophenyl, dibenzofuran-yl, dibenzothiophen-yl, furanyl, indolyl, pyridazinyl, pyrazinyl, pyrimidinyl may be substituted by heteroatoms selected from the group consisting of nitrogen, sulfur or oxygen , Thiazolyl, triazolyl or quinolinyl.
  • Protected formyl in the context of the invention is a formyl radical which is protected by conversion into an aminal, acetal or a mixed aminal acetal, where the aminals, acetals and mixed aminal acetals can be acyclic or cyclic.
  • Protected hydroxy in the context of the invention is a hydroxy radical which is protected by conversion into an acetal, carbonate, carbamate or carboxylate. Examples thereof are the conversion into a tetrahydropyranyl adduct, into a benzyloxycarbonyl, allyloxycarbonyl or a tert-butyloxycarbonyl derivative.
  • steps b1) and b2) are, of course, preferably carried out in one reaction.
  • compounds of formula (II) are used for the preparation of compounds of formula (I), preferably the compounds of formula (VII) in a conventional manner, for example by reaction with a chiral auxiliary reagent or by continuous or discontinuous chromatography when enantiomers on a chiral column material in the stereoisomers.
  • the ether cleavage according to step a) can be carried out, for example, in a manner known per se by reaction with BBr 3 and subsequent treatment with water.
  • reaction of the compounds of the formula (III) with compounds of the formula (IV) in step b1) and the reaction of the compounds of the formula (V) with compounds of the formula (VI) in step b2) are preferably carried out in organic solvent in the presence of bases carried out.
  • Particularly suitable solvents are alcohols such as, for example, methanol, ethanol, propanol, ethylene glycol or ethylene glycol monomethyl ether and amide solvents such as e.g. N, N-dimethylformamide, N, N-dimethylacetamide or N-methylpyrrolidone or mixtures of the solvents mentioned.
  • alcohols such as, for example, methanol, ethanol, propanol, ethylene glycol or ethylene glycol monomethyl ether
  • amide solvents such as e.g. N, N-dimethylformamide, N, N-dimethylacetamide or N-methylpyrrolidone or mixtures of the solvents mentioned.
  • bases examples include alkali metal and alkaline earth metal compounds such as oxides, hydroxides, carbonates or alkoxides, for example: calcium oxide, sodium hydroxide, potassium carbonate or sodium methoxide. It is also possible to use tertiary amines such as e.g. Use triethylamine or tributylamine as bases.
  • the molar ratio between the compound of the formula (III) or (V) used and the compound of the formula (IV) or (VI) is preferably between 1: 1 and 1: 1.5 or 1: 2 and 1:10 for identical ones Compounds of formulas (IV) and (VI); In general, a complete excess of compounds of the formulas (IV) or (VI) is also sufficient for complete reaction.
  • the base is preferably used in at least an equivalent amount to the compound of the formulas (III) or (V). When using insoluble in the solvent bases, such as potassium carbonate in DMF, it is expedient to use four to ten times the molar amount and at the same time to ensure intensive mixing of the suspension.
  • the reaction according to step b) can also be carried out in a two-phase system, wherein the non-aqueous phase used are solvents in which the resulting product of the formulas (V) or (VII) is at least predominantly soluble.
  • the non-aqueous phase used are solvents in which the resulting product of the formulas (V) or (VII) is at least predominantly soluble.
  • dichloromethane is suitable for this purpose.
  • phase transfer catalysts such as e.g. to use quaternary ammonium or phosphine salts and tetrabutylammonium salts. Preference is given to tetrabutylammonium salts.
  • reaction temperature in the reaction of compounds of the formula (III) for the preparation of the compounds of the formula (IV) may, for example, in the range of about 20 ° C to 100 ° C, preferably in the range of 20 ° C to 80 ° C.
  • reaction of compounds of formula (V) for the preparation of the compounds of formula (VII) may, for example, in the range of about 20 ° C to 100 ° C, preferably in the range of 20 ° C to 80 ° C.
  • step c) The reduction of the compounds of the formula (VII) to the compounds of the formula (I) in step c) is preferably carried out by methods known per se, for example by reaction with trichlorosilane in inert solvents such as toluene or xylene and in the presence of tertiary amines such as tri -nbutylamine at reflux temperature, (see, eg EP-A 398 132 . EP-A 749 973 such as EP-A 926,152 ).
  • the compounds of formula (I), preferably in stereoisomerically enriched form, are particularly useful as ligands for the preparation of transition metal complexes which can be used as catalysts for processes for preparing enantiomerically enriched compounds.
  • the invention includes both transition metal complexes containing compounds of formula (I), as well as catalysts containing the transition metal complexes of the invention.
  • Preferred transition metal complexes are those which are obtainable by reacting compounds of the formula (I) in the presence of transition metal compounds.
  • Preferred transition metal compounds are compounds of rhodium, iridium, ruthenium, palladium and nickel, with those of rhodium, iridium and ruthenium being more preferred.
  • transition metal compounds cyclopentadienyl 2 Ru, Rh (acac) (CO) 2 , Ir (pyridine) 2 (1,5-cyclooctadiene) or polynuclear bridged complexes such as [Rh (1,5-cyclooctadiene) Cl] 2 and [ Rh (1,5-cyclooctadiene) Br] 2 , [Rh (ethene) 2 Cl] 2 , [Rh (cyclooctene) 2 Cl] 2 , [Ir (1,5-cyclooctadiene) Cl] 2 and [Ir (1, 5-cyclooctadiene) Br] 2 , [Ir (ethene) 2 Cl] 2 , and [Ir (cyclooctene) 2 Cl] 2 .
  • transition metal complexes such as, for example, those of the formulas (IXa-c) and (Xa-e) and transition metal complexes prepared in situ, the latter being preferred.
  • the transition metal complexes and catalysts for asymmetric hydrogenations are preferably used.
  • Particularly preferred asymmetric hydrogenations are hydrogenations of prochiral ketones, in particular alpha- and beta-keto esters, such as, for example, acetoacetic esters or chloroacetoacetic esters.
  • the amount of the transition metal compound or the transition metal complex used can be, for example, 0.001 to 5 mol%, based on the substrate used, preferably 0.01 to 2 mol%.
  • the enantiomerically enriched compounds which can be prepared according to the invention are particularly suitable for the production of agrochemicals, pharmaceuticals or intermediates thereof.
  • the advantage of the present invention is that enantioselectivities and activities are achieved with the aid of the catalysts according to the invention, which have hitherto not been achievable with similar catalysts.
  • the phosphine oxide from Example 2a (0.686 g, 0.86 mmol) was initially charged with xylene (18 ml) under argon, the resulting mixture was initially treated with tri- (n-butyl) amine (3.5 ml, 15 mmol) and trichlorosilane ( 1.5 ml, 15 mmol) and then heated at reflux for 2 hours. It was allowed to cool, briefly stirred with degassed NaOH solution (30%, 15 ml), 25 ml of degassed water added and the phases were separated. The aqueous phase was extracted 3 times with methyl tert-butyl ether (10 ml) and the combined organic phases were washed first with sat. Brine and then dried over MgSO 4 . The organic solvent was removed in vacuo to give the product as a colorless powder. Yield: 95% of theory 31 P NMR: - 13.4 ppm.
  • Example 2b The phosphine oxide from Example 2b was reduced completely analogously to Example 5 and obtained in a yield of 92%.
  • Example 3b The phosphine oxide from Example 3b was reduced completely analogously to Example 5 and obtained in a yield of 91%.
  • Example 4 The phosphine oxide from Example 4 was reduced completely analogously to Example 5 and obtained in a yield of 94%.

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Claims (8)

  1. Composés de formule (I)
    Figure imgb0021
     où
    B représente CHR1 où R1 représente l'hydrogène ou C1-C4-alkyle et
    R2 représente méthyle, éthyle, n-propyle, isopropyle, n-butyle ou tert.-butyle et R3 représente C1-C6-alkyle ou B-COOR2 et
    G représente le chlore ou l'hydrogène et
    R' et R" représentent chacun indépendamment les uns des autres, ou chacun de manière identique, C3-C8-alkyle ou C5-C10-aryle qui est non substitué, ou substitué une fois ou plusieurs fois avec des groupements qui sont choisis dans le groupe chlore, fluor, cyano, phényle, C1-C6-alcoxy et C1-C6-alkyle, de manière particulièrement préférée représentent cyclopentyle, cyclohexyle, cycloheptényle, phényle, o-, m-, p-tolyle, 3,5-diméthylphényle, 3,5-di-tert.-butylphényle, 3,5-diméthyl-4-méthoxyphényle, 3,5-di-tert.-butyl-4-méthylphényle, 4-trifluorométhylphényle, 4-fluorophényle, 2-, 3-furyle, 2-, 3-thiophényle, 2-N-méthyl-pyrrolyle, N-méthyl-2-indolyle et 2-thiazolyle.
  2. Composés selon la revendication 1 suivants :
    (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-méthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-phényl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-éthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-phényl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(méthoxycarbonyl-méthoxy)-biphényl-2,2'-diyl]-bis-[(di-phényl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(éthoxycarbonyl-méthoxy)-biphényl-2,2'-diyl]-bis-[(di-phényl)phosphine, (R)- et (S)-[5,5'-dichloro-6-(méthoxycarbonyl-méthoxy)-6'-(cyclohexyloxy)-biphényl-2,2'-diyl]-bis[(di-phényl)phosphine, (R)- et (S)-[5,5'-dichloro-6-(éthoxycarbonylméthoxy)-6'-(cyclohexyloxy)biphényl-2,2'-diyl]-bis-[(di-phényl)phosphine,
    (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-méthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-cyclohexyl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-éthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-cyclohexyl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(méthoxycarbonyl-méthoxy)-biphényl-2,2'-diyl]-bis-[(di-cyclohexyl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(éthoxycarbonyl-méthoxy)-biphényl-2,2'-diyl]-bis-[(di-cyclohexyl)phosphine, (R)- et (S)-[5,5'-dichloro-6-(méthoxycarbonyl-méthoxy)-6'-(cyclohexyloxy)biphényl-2,2'-diyl]-bis-[(di-cyclohexyl)phosphine, (R)- et (S)-[5,5'-dichloro-6-(éthoxycarbonyl-méthoxy)-6-(cyclohexyloxy)biphényl-2,2'-diyl]-bis-[(dicyclohexyl)phosphine,
    (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-méthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butyl-4-méthoxyphényl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-éthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butyl-4-méthoxyphényl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(méthoxycarbonyl-méthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butyl-4-méthoxyphényl)-phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(éthoxycarbonyl-méthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butyl-4-méthoxy-phényl)phosphine, (R)- et (S)-[5,5'-dichloro-6-(méthoxycarbonyl-méthoxy)-6'-(cyclohexyloxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butyl-4-méthoxy-phényl)phosphine, (R)- et (S)-[5,5'-dichloro-6-(éthoxycarbonyl-méthoxy)-6'-(cyclohexyloxy)biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butyl-4-méthoxyphényl)phosphine,
    (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-méthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-diméthyl-4-méthoxyphényl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-éthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-diméthyl-4-méthoxyphényl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(méthoxycarbonyl-méthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-diméthyl-4-méthoxyphényl)phosphine,
    (R)- et (S)-[5,5'-dichloro-6,6'-bis(éthoxycarbonylméthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-diméthyl-4-méthoxyphényl)phosphine, (R)- et (S)-[5,5'-dichloro-6-(méthoxycarbonyl-méthoxy)-6'-(cyclohexyloxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-diméthyl-4-méthoxyphényl)phosphine, (R)- et (S)-[5,5'-dichloro-6-(éthoxy-carbonyl-méthoxy)-6'-(cyclohexyloxy)biphényl-2,2'-diyl]-bis-[(di-3,5-diméthyl-4-méthoxyphényl)phosphine,
    (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-méthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butylphényl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-éthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butylphényl)-phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(méthoxycarbonylméthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butylphényl)phosphine, (R) et (S)-[5,5'-dichloro-6,6'-bis(éthoxycarbonyl-méthoxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butylphényl)phosphine, (R)- et (S)-[5,5'-dichloro-6-(méthoxycarbonyl-méthoxy)-6'-(cyclohexyloxy)-biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.-butylphényl)phosphine, (R)- et (S)-[5,5'-dichloro-6-(éthoxycarbonylméthoxy)-6'-(cyclohexyloxy)biphényl-2,2'-diyl]-bis-[(di-3,5-di-tert.butylphényl)phosphine,
    (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-méthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-4-fluorophényl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis(1-éthoxycarbonyl-éthoxy)-biphényl-2,2'-diyl]-bis-[(di-4-fluorophényl)phosphine,
    (R)- et (S)-[5,5'-dichloro-6,6'-bis(méthoxycarbonyl-méthoxy)-biphényl-2,2'-diyl]-bis-[(di-4-fluorophényl)phosphine, (R)- et (S)-[5,5'-dichloro-6,6'-bis-(éthoxycarbonyl-méthoxy)-biphényl-2,2'-diyl]-bis-[(di-4-fluorophényl)phosphine,
    (R)- et (S)-[5,5'-dichloro-6-(méthoxycarbonyl-méthoxy)-6'-(cyclohexyloxy)-biphényl-2,2'-diyl]-bis-[(di-4-fluorophényl)phosphine et (R)- et (S)-[5,5'-dichloro-6-(éthoxycarbonyl-méthoxy)-6'-(cyclohexyloxy)biphényl-2,2'-diyl]-bis-[(di-4-fluorophényl)phosphine,
    ainsi que les composés analogues non substitués en position 5,5' et dans le cas d'un centre stéréogène dans les groupements liés en position 6 et/ou 6' également les composés correspondants de configuration (R) et (S) dans les groupements cités.
  3. Procédé de production de composés selon l'une des revendications 1 et 2 caractérisé en ce que
    • dans une étape a)
    des composés de formule (II)
    Figure imgb0022
     sont convertis par clivage d'éther en composés de formule (III)
    Figure imgb0023
    • dans une étape b1)
    les composés de formule (III) sont convertis par réaction avec des composés de formule (IV)

            R3-Akt     (IV)

    en présence de base en composés de formule (V)
    Figure imgb0024
    • dans une étape b2)
    les composés de formule (V) sont convertis par réaction avec des composés de formule (VI)

            R2OOC-B-Akt     (VI)

    en présence de base en composés de formule (VII)
    Figure imgb0025
    • et dans une étape c)
    les composés de formule (VII) sont réduits en composés de formule (I),
    où, dans les formules citées, B, R2, R3, G, R' et R" possèdent les significations qui ont été définies pour la formule (I) dans la revendication 1 et
    Akt représente un halogène ou un sulfonate et
    R4 dans la formule (II) représente C1-C6-alkyle.
  4. Composés de formule (VII)
    Figure imgb0026
     où B, R2, R3, G, R' et R" possèdent les significations qui ont été définies pour la formule (I) dans la revendication 1.
  5. Composés de formule (V)
    Figure imgb0027
     où R3, G, R' et R" possèdent les significations qui ont été définies pour la formule (I) dans la revendication I.
  6. Complexes de métaux de transition contenant des composés de formule (I) selon la revendication 1.
  7. Catalyseurs contenant des complexes de métaux de transition selon la revendication 6.
  8. Procédé pour la production catalysée par des métaux de transition de composés énantiomériquement enrichis caractérisé en ce que des catalyseurs selon la revendication 7 sont utilisés comme catalyseurs.
EP04021174A 2003-09-16 2004-09-07 Phosphines chirales pour utilisation en synthèse asymétrique Expired - Lifetime EP1516880B1 (fr)

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DK350383A (da) * 1982-08-27 1984-02-28 Hoffmann La Roche Phosphorforbindelser
US4879416A (en) * 1987-11-23 1989-11-07 Eastman Kodak Company Preparation of bidentate ligands
US5110955A (en) * 1989-04-14 1992-05-05 Hoffmann-La Roche Inc. Tocopherol synthesis: chromane cyclization and catalysis
JP3369561B2 (ja) * 1992-01-31 2003-01-20 エフ・ホフマン−ラ ロシユ アーゲー 燐化合物
DE19522293A1 (de) * 1995-06-20 1997-01-02 Bayer Ag Neue Bisphospine als Katalysatoren für asymmetrische Reaktionen
EP1002801B1 (fr) * 1998-11-19 2003-06-18 Solvias AG Diphenyldiphosphines chirales et leurs complexes métalliques d-8
EP1078632A1 (fr) * 1999-08-16 2001-02-28 Sanofi-Synthelabo Utilisation des inhibiteurs de monoamine oxydases dans la fabrication d'un médicament contre l'obésité
DE60027734T2 (de) * 1999-09-20 2007-04-05 The Penn State Research Foundation Chirale phosphine, deren komplexe mit übergangsmetallen und deren verwendung in asymmetrischen synthesereaktionen
WO2004031110A2 (fr) * 2002-10-01 2004-04-15 Dieter Arlt Isomerisation de derives homogenes chiraux de o,o'-dihydroxy-biphenyle
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JP4902952B2 (ja) 2012-03-21
DE502004008727D1 (de) 2009-02-05
EP1516880A1 (fr) 2005-03-23
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